Effects Of Anti-fetal Immunity On The Pathogenesis Of Hypertensive Disorder Complicating Pregnancy

Hypertensive disorder complicating pregnancy (HDCP) is still a serious threaten to maternal-fetal health, which is contributed to the high maternal-fetal perinatal morbidity worldwide. A lot of studies have shown that immune imbalance occurs in HDCP. To maintain normal pregnancy, the coordination of cell-mediated immunity and humoral immunity is needed. Many reports indicated that cell-mediated immunity involved in the pathogenesis of HDCP. And most of them focused on the effects of serum cytokine profiles. However, there is lack of data about the effects of humoral immunity on the pathogenesis of HDCP. In the present study, the actual status of humoral immunity in HDCP was explored in view of both mother and fetus. It aimed to explore the effects of anti-fetal immunity on the pathogenesis of HDCP. Objective To detect the anti-HLA antibodies in peripheral blood of women with HDCP and normal term pregnancy, and compare if the antibody specificity was consistent with the HLA genotype of fetus. To evaluate if the HLA antibodies were activated by fetal-derived antigens, illustrating the possible role of maternal anti-fetal immunity in the pathogenesis of HDCP.Methods 60 patients with HDCP were divided into 3 groups, including gestational hypertension group, light pre-eclampsia group and severe pre-eclampsia group. 46 normal term pregnant women were selected as control group. Flow PRA was applied to screen the HLA antibodies in serum. For those women with positive results, the antibody specificity was further determinated by Luminex assay. Meanwhile, the HLA phenotypes of the mother and fetus were detected by SSP-PCR. It was compared if the HLA antibody specificity was in consistent with the HLA genotypes.Results The positive rate of anti-HLA classⅡantibody in maternal peripheral blood of normal term pregnancy was 6.5%, while it was 20% in gestational hypertension group, 20% in pre-eclampsia group and 25% in severe pre-eclampsia group. The difference was statistically significant (P < 0.05). The positive rate of anti-HLA class I in maternal peripheral blood of normal term pregnancy was 19.6%, while it was 20% in gestational hypertension group, pre-eclampsia group and severe pre-eclampsia group, respectively. There was no significant difference (P > 0.05). The fetal HLA genotypes were in good consistence with the specificity of anti-HLA class II antibody in maternal peripheral blood.Conclusion The positive rate of the anti-HLA classⅡantibodies in HDCP groups was increased, which was activated by the fetal-derived antigens. Objective To compare the percentage of IL-6 positive monocytes in fetal cord blood of normal term pregnant women and patients with HDCP, finding out the activation status of fetal monocytes.Methods 60 patients with HDCP were divided into 3 groups, including gestational hypertension group, light pre-eclampsia group and severe pre-eclampsia group. 46 normal term pregnant women were selected as control group. The cord mononuclear cells (CBMC) were isolated by density gradient centrifugation and stained with FITC-CD14 and PE-IL-6 monoclonal antibodies. The percentage of IL-6 positive monocytes in cord blood was determined by flow cytometry.Results The percentage of IL-6 positive monocytes in cord blood of normal group was 0.78%±0.54%; while it was 4.38%±0.91% in the gestational hypertension group, 5.73%±2.18% in light pre-eclampsia and 6.29%±2.70% in severe pre-eclampsia. The difference was statistically significant (P < 0.01). Moreover, the percentage of IL-6 positive monocytes was increased along with the progression of the disease (P < 0.05).Conclusion The fetal monocytes were activated in patients with HDCP and increased with the progression of the disease. Objective To explore the role of anti-fetal HLA antibody-secreting memory B cells in HDCP.Methods 60 patients with HDCP were divided into 3 groups, including gestational hypertension group, light pre-eclampsia group and severe pre-eclampsia group. 46 normal term pregnant women were selected as control group. The CBMC were isolated by density gradient centrifugation. The B cell lysate was obtained by stimulating the CBMC with IFN-γfor 72 h, which was applied as the fetal antigens. The PBMC were stimulated with PWM and cultured in vitro, which owned the ability to produce HLA antibodies. The frequency of anti-HLA antibody secreting memory B cells were detected by ELISPOT assay.Results In control group, the frequency of anti-fetal-HLA secreting memory B cell was 0.37%±0.13%; while it was 0.67%±0.11% in gestational hypertension group, 0.79%±0.21% in light pre-eclampsia group and 0.94%±0.27% in severe pre-eclampsia group. The difference was statistically significant (P < 0.01). The difference between gestational hypertension group and severe pre-eclampsia group was statistically significant (P < 0.05). However, there was no statistically significant between gestational hypertension group and light pre-eclampsia group (P > 0.05).Conclusion The frequency of anti-fetal HLA antibody secreting B cells was increased in HDCP, which might be the cause of enhanced humoral immunity.